NLRP3炎症小体与心房颤动的相关性研究

2017-02-16许键何燕罗蓓蓓向春林黄艳群舒成霖王蓉

中国循环杂志 2017年1期

关键词：水平

许键，何燕，罗蓓蓓，向春林，黄艳群，舒成霖，王蓉

NLRP3炎症小体与心房颤动的相关性研究

许键，何燕，罗蓓蓓，向春林，黄艳群，舒成霖，王蓉

目的：通过检测心房颤动（房颤）患者外周血NLRP3的表达水平，探讨 NLRP3炎症小体与房颤的相关性。

心房颤动；炎症介导素类

Method: A total of 60 AF patients were enrolled and divided into 2 groups: Paroxysmal AF (PAF) group and Non-paroxysmal atrial fibrillation (nPAF) group, n=30 in each group; in addition, there was a Control group including 26 healthy subjects from physical examination. NLRP3 expression in peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry; blood levels of IL-1β, IL-6, CRP and NT-proBNP were detected by ELISA. The correlations among different factors were studied by liner regression analysis and the differences were compared among groups.

Result:①Compared with Control group, PAF and nPAF groups had increased PBMCs level of NLRP3 and blood levels of IL-1β, IL-6, CRP, NT-proBNP, P＜0.05, while NLRP3 level was similar between PAF group and nPAF group, P＞0.05.②PAF and nPAF groups showed elevated blood level of NT-proBNP than Control group, P＜0.05. ③PBMCs level of NLRP3 was positively related to left atrial diameter (r=0.579, P＜0.05) and negatively related to left ventricular ejection fraction (r=-0.490, P＜0.05) in both AF groups.

Conclusion:①NLRP3 inflammasome was closely related to AF, which may provide a therapeutic target for AF treatment.②AF was closely related to inflammatory response.③Downstream product of NLRP3 may cause the inflammatory response which could induce the occurrence, development and maintenance of AF in relevant patients.

Key wordsAtrial fibrillation; Inflammatory mediators

(Chinese Circulation Journal, 2017,32:72.)

心房颤动（房颤）是临床最常见的心律失常之一，目前全球房颤人数估计为3 350万人，预计2060年房颤患病人数将再增加2倍[1]，其主要危害是脑卒中和外周血管栓塞等并发症，已成为心血管疾病发病和死亡的主要原因之一[2]。迄今为止，房颤的发生机制尚未完全阐明，现有大量证据显示炎症与房颤密切相关[3-5]。

炎症小体属于胞浆型模式识别受体（PRR），由多种蛋白质组成的蛋白复合体，它通过半胱天冬氨酸酶（Caspase-1）调控白细胞介素（IL）-1β前体（pro-IL-1β）、IL-18前体（pro-IL-18）、IL-33前体（pro-IL-33）等，促使其转化为有活性的IL-1β、IL-18及IL-33等，进而参与天然免疫系统的激活[6，7]。NLRP3炎症小体由NLRP3、凋亡相关斑点样蛋白（ASC）和Caspase-1组成，NLRP3是NLRP3炎症小体多种蛋白质成分中最核心的组成部分。国内外研究表明，NLRP3炎症小体在心肌缺血再灌注、心肌梗死及心力衰竭等多种心血管疾病中发挥重要的作用，具有极高的临床研究价值[8]。现有证据表明，炎症可能通过影响心脏的电重构和（或）心肌重构，参与了房颤的发生、发展。本课题将研究NLRP3在房颤患者外周血单核淋巴细胞（PBMCs）中的表达水平，探究 NLRP3炎症小体与房颤患者临床指标的相关性，探究房颤发生的预警信号和潜在干预靶点。